Pancreatic cancer is rapidly fatal in the majority of patients, partly because of the difficulty of early diagnosis. Since the most common histologic type of primary carcinoma of the excorine pancreas is duct cell adenocarcinoma, elucidation of organ-specific and cell-type specific tumor-associated antigens in the human exocrine pancreas is needed. Recently, a series of monoclonal antibodies recognizing pancreatic adenocarcinoma cells has been produced in our laboratory. One of these antibodies, YPan1, may be particularly useful in determining the cellular origin of pancreatic carcinoma and in diagnosing the disease because of the following reasons: 1) It is produced in high titer. 2) Among cultured cancer cells, it is specific for pancreatic cell lines. 3) Among normal tissues, it is specific for pancreas. 4) In normal pancreas, only ducts and ductules, and not acinar cells, recognized. 5) In immunohistochemical studies, the antigen is neuraminidase-sensitive and found on membranes, in cytoplasm, and in intraluminal contents. Preliminary results suggest that the YPan1 antigen is a pancreatic mucin secreted by cultured pancreatic cancer cells. Because of the mucin-like properties of YPan 1 antigen and because so little is known about the biochemistry and immunology of pancreatic mucin, we plan to focus our research efforts on the isolation and characterization of human pancreatic mucin in normal and cancerous tissues and cells, and on the YPan1 mucin antigen in particular. Pancreatic mucin will be purified from cells, culture media, and nude mouse xenografts of human pancreatic cancer cells, and its immunological reactivity with YPan1 and other antibodies, its carbohydrate and peptide structure will be investigated chemically. We plan to use the results of these studies to investigate the synthesis and secretion of pancreatic mucin, to compare the mucins present in cell lines of different degrees of differentiation and in normal and diseased tissues, and to evaluate the usefulness of immunoassay for early detection and diagnosis of pancreatic cancer. These studies may prove useful not only in understanding the histogenesis of pancreatic cancer, but also in its diagnosis and therapy.